Infectious disease Flashcards
Bacteriology, virology
What are the 3 potential routes of infection affecting the nervous system?
- Direct extension e.g. from otitis interna or sinusitis
- Bacterial embolisation within the brain
- Bacterial penetration through BBB
List the potential causes of meningitis, encephalitis and meningoencephalitis
- Bacteria
- viruses
- fungi
- Protozoa
- Rickettsia
- Parasite migrations
- Chemical agents
- Idiopathic or immune mediated diseases
List the ways in which pathology of the nervous system can occur
- Invasion of neuronal tissue by pathogenic agent
- Induction of an immune response
- Toxin or drug getting into and interacting with the nervous system
How may a pathogenic agent invade the neuron tissue?
- Direct invasion of peripheral nerves
- From adjacent structures such as the meninges
- From blood (haematogenous)
Explain how an immune response can cause pathology of the nervous system
- Inflammation and damage
- Potential for auto-immune response
Explain how a toxin or drug may cause pathology of the nervous system
- Block signalling
- Damage specific cells
- Toxicoinfectious deliver involving infection
Explain how toxicoinfectious delivery may occur
- Toxins must pass through barriers or be released near site of action
- Species differences in susceptibility
- e.g. If receptors present on gut wall, toxin may bind to cell wall, but if not present may pass through the wall and target internal site
Describe the normal microbiology of the CNS
- CNS sterile
- To cause disease, organisms, toxins or drugs need to enter CNS
- BBB effective so incidence of infection is low
What are the different pathways of breach of the BBB?
- Transcellular (through the cell)
- Paracellular (breaking of endothelial bonds and passage between cells)
- Intracellular: use of other cells in order to get into the neuro tissue
Give an example of intracellular breach of the BBB and what this means for treatment
- Listeria
- Uses leukocytes as a route through neuro tissue
- No damage to BBB
- Higher concentration of antibiotics required to treat
How can infection of the CNS be detected?
- Clinical signs
- Physical effects
- Imaging
- Samples
List the clinical signs of CNS infection
- Depression
- Pyrexia
- Cervical pain
- Hyperaesthesia
- Photophobia
- Generalised rigidity
- Seizures
- Paralysis (local and general)
- Ataxia
- Papilloedema
- Possible ophthalmic inflammation
- Systemic signs e.g. septic shock, bradycardia
List the parameters within CSF that can be assessed with regards to infection of the nervous system, and give examples of what changes may indicate
- Glucose (measured as % of blood glucose, reduced in meningitis)
- Specific gravity (increased with cell proteins)
- Intracranial pressure
- Immunology (antibody titres to agents and cytology)
- Microbiology (staining)
- Enzyme analysis for cell breakdown (but not necessarily duet= to infection)
What would a CSF sample with RBCs present but clear supernatant indicate?
Iatrogenic contamination of sample
What would a CSF sample with RBCs present and erythophagocytosis or crenated RBCs indicate?
Intrathecal haemorrhage
What would a CSF sampe with elevated monomuclear pleocytosis indicate?
Viral and immune mediate disorders
What would a CSF sample with neutrophilic pleocytosis and healthy neutrophils indicate?
Necrotic CNS tumours or immune-mediated disease
What would a CSF sample with neutrophilic pleocytosis of degenerative/toxic neutrophils indicate?
- Bacterial meningitis
- Abscess
- Necrotic CNS tumours
- Cellular degeneration due to poor sample handling
What would a CSF sample with eosinophilic pleocytosis indicate?
Parasitic/fungal/protozoal diseases or eosinophilic meningoencephalomyelitis
What would a CSF sample with elevated lymphoblasts indicate?
CNS lymphoma
List the microbial tests that can be used in the investigation of neurological infectious diseases
- Gram stain on CSF smears
- Culture and sensitivity assays
- Antigen tests on CSF fluid
- ELISA for pathogen/toxin
- Molecular tests e.g. PCR
Identify the common underlying causes of meningitis and encephalitis
- Direct extensions from sinusitis,otitis media or interna, vertebral osteomyelitis and discospondylitis
- Which can be secondary events to migrating grass awns, other foreign bodies, deep bite wounds, iatrogenic infections
List the common aerobic bacteria in the dog that cause neurological disease
- Pasteurella multocida
- Staphylococcus spp.
- E. coli spp.
- Streptococcus spp.
- Actinomyces spp.
- Nocardia spp.
List the common anaerobic bacteria in the dog that cause neurological disease
- Bacteroides spp.
- Peptostreptococcus anaerobicus
- Fusobacterium spp.
- Eubacterium spp.
- Propionbacterium spp.
What are common sources of nervous system infection in the dog?
Endocarditis and septicaemia
Describe the prognosis for bacterial infection of the nervous system in dogs
Guarded even with treatment, relapse common and prolonged therapy may be required
Outline the treatment of bacterial meningitis or encephalitis in the dog
- Appropriate use of antibiotics according to culture and serology results
- Selection of broad spec antibiotics thaat can penetrate BBB e.g. ampicillin, metronidazole, tetracyclines, trimethoprim-sulfates, fluoroquinoles, 3rd gen cephalosporins
- Bacteriocidal where possible
- May need higher dose if BBB still in tact
Describe streptococcal meningitis in pigs (pathogen, conditions, epidemiology, prognosis)
- Streptococcus suis
- Meningitis, arthritis septicaemia, bronchopneumonia
- Systemic disease that gets into the brain
- Disease outbreak common in intensively reared
- Meningitis often fatal, characterised by fever
Describe bastard strangles
- Streptococcus equi
- Extension of upper resp. tract and lymphatic infection that leads to abscessation in many organs incl. nervous tissue
- ~ 1% strangles
How does discospondylitis commonly develop?
Bacteraemia, which may be from septic foci in other systems and may be a result of some clinical procedures such as surgery, dental work
List fungal agents that may cause discospondylitis in dogs and indicate the prevalence
- Less frequent than bacterial cause
- Aspergillus spp (most common)
- Paecilomyces varioti
- Mucor spp.
- Fusarium spp.
Explain how bacteria can accumulate in the blood vessels of the vertebrae
- In metaphysis (young)/epiphysis (adult) arterial capillaries form narrow loop with concavity directed towards feeding artery
- Narrow loop, sudden change in diameter from fine arterial capillary to large venous sinus leads to slowed blood flow and increased turbulence
- Microogranisms accumulate in efferent loop, aided by reduced concentration of phagocytic cells here
- Followed by initial inflammatory reaction leading to formation of microthrombus
Describe the pathogenesis of bacterial discospondylitis following the establishment of infection
- Tissue necrosis and bone destruction
- Perpetuated by:
1: Mutliplication of pathogen
2: Lytic nature that exudate acquires due to elevated local lysosomal activity
3: Ischaemic damage due to accumulation of exudate in rigid structure
4: Subarachnoid abscess in some cases
What is the consequence of host defences responding to devitalised tissue in discospondylitis?
Tissue becomes surrounded by granulation tissue
Following the initial bone destruction in discospondylitis, how does the disease progress?
- Invasion of subchondral bone tissue and eventually the intervertebral disc
- Accumulate exudate may diffuse to veretbral canal or paravertebral soft tissue, destroying osteocytes and vascular structures
How may the propagation of the infection in discospondylitis affect the spinal cord?
- By the action of the exudate
- By the growth of granulation tissue
- Potential for spinal compression
What approach should be taken if there is no response to appropriate antibacterial treatment for discospondylitis?
- Reconsider diagnosis, consider aspergillosis for example
- If no response to treatment after that, surgery
Describe the properties of Listeria monocytogenes (appearance, growth conditions, metabolic activity)
- Gram +ve rod
- grow on non-enriched media
- Tolerate wide range of pH and temperatures
- Small haemolytic colonies on BA
- Facultative anaerobes, catalase positive, oxidase negative
Describe the pathogenesis of infection with Listeria monocytogenes
- Contaminated feed
- Possible septicaemia, encephalitis, abortion, sepsis, meningitis
- Meningitis often complicated by encephalitis
- Ocular infections common
Describe the neurotropic spread of Listeria monocytogenes
- Enters mammalian cells via induced phagocytosis
- Can escape vacuole
- Propel self using actin polymerisation
- Spread from cell to cell
- Can ascend nervous tissue from oral cavity infection to CNS
Outline the clinical signs of Listeria monocytogenes
- Characteristic neurological signs, abortion
- Dullness, circling, tilting of head, facial paralysis
- Unilateral facial paralysis resulting in drooling, dropping of eyelids and ears
- In ruminants: encephalititis, abortion, septicaemia, endophthalmitis
What is the incubation period for neural listeriosis?
14-40 days
Identify potential diagnostic specimens for Listeria monocytogenes in the following scenarios
a: neurological signs
b: abortion
c: septicaemia
a: CSF fluid from medulla or pons
b: cotyledons, foetal abomasal/uterine discharge
c: fresh liver, spleen or blood
Describe the potential findings in diagnostic samples positive for Listeria monocytogenes
- Smears: G+ve rods
- Immunofluorescence
- Histologically may see microabscesses and heavy perivascular mononuclear cuffing
- White cell numbers ?1.2x10^7
Outline the prevention for Listeria monocytogenes
- Vaccines ineffective
- Feed method that reduces ocular contact
- Ensure good quality silage fed
Give examples of toxin producing bacteria
- Clostridium tetani (tetanus)
- Clostridium botulinum (botulism)
- E. coli (oedema disease)
Give an example of a toxin that is produced symbiotically on pasture
Acremonium loliae fungal endophyte, leads to rye grass staggers, sporadic in UK
Give the organism, toxin effect and species affected by focal symmetrical encephalomalacia
- Clostridium perfringes type D
- Causes vasculopathy, encephalomalaxcia
- Affects sheep/lambs and goats
Describe the sampling requirements for the diagnosis of clostridial infection
- Fastidious anaerobes, samples must be kept anaerobic
- samples must be from live/recently dead animals as Clostridia increase in putrifying body
- Culture promptly under anaerobic conditions
- Wear gloves, toxins potent
- Blood culture not performed generally
Describe the morphology of Clostridia
- Drumstick appearance
- All form endospores
- G+ve rods, relatively large
Compare C. tetani and C. botulinum based on:
a: the site of toxin production
b: genes that regulate the production
c: antigenic type
d: mode of action of toxin
a: T: in wounds, B: in carcasses, decaying veg, canned foods, can be toxicoinfectious
b: T: on plasmids, B: usually genome
c: T: one type, tetanospasmin, B: 8 distinct types A to G
d: T: synaptic inhibition, B: inhibition of neuromuscular junction
How are C tetani and C botulinum generally differentiated from one another?
- Colonial morphology
- Biochemistry
- Toxin identification
- Molecular tests
Describe toxicoinfectious botulism
- IN horse, Clostridium grows in GIT and produces toxin in vivo = shaker foal in USA
- Can colonise in wounds and produce toxin
Which antigenic types of botulinum toxin cause the most outbreaks in domestic animals?
Ca/b and D
Outline the treatment and control of botulism
- Antitoxins available, neutralise circulating toxins but not effective once toxin enters nerve terminal
- Guanidine ydrochloride to enhance neurotransmitter release
- Vaccine available for horses and cattle in endemic areas
- removal of suspect food stuff
Describe the mechanism of action of the botulinum toxin
- Acts at NMJ
- Stops stimulation and leads to flaccid paralysis, toxin absorbed from GIT
- Circulates blood
- Acts at NMJs of cholinergic nerves and peripheral autonomic nerve synapses
- Binds somatic and autonomic nerve terminals
- Inhibits neurotransmitter release
- Death from paralysis of respiratory muscles
Describe the mechanisms of action of the tetanus toxin
- Blocks inhibitor neurotransmitter release triggering spastic paralysis
- Binds ganglioside receptors on motor neurones
- Then moves into vesicles via axonal transport to nerve body and dendritic processes
- Toxin then transfers trans-synaptically to inhibitory neurones where it interacts with and blocks vesicle docking and inhibitory NT release is blocked
What is the incubation period for tetanus?
5-10 days
Describe the clinical signs of tetanus
- Stiffness
- Local spasms
- effects on heart and resp rate
- dysphagia
- Altered facial expression
Outline the diagnosis of tetanus
- Usually presumptive based on clinical signs
- Differentiate from strychnine poisoning
- Gram smears, look for characteristic drumstick forms of C tetani
Describe the treatment of tetanus
- Antitoxin administration
- Large doses of penicillin IM
- Debridement of wounds (potentially use hydrogen peroxide wash)
Outline the control options for tetanus
- Vaccination of at risk animals (common)
- Debridement of wounds
- Passive antitoxin in unvaccinated animals
How long is the incubation period for botulism?
3-17 days after ingestion
Describe the clinical signs of botulism
- Dilated pupils
- Dry mucous membranes
- Decreased salivation
- Tongue flaccidity
- Dysphagia
Outline the diagnosis of botulism
- Mainly based on clinical signs and food intake history
- Confirmation by detection of toxin in serum (not confirmed method)
List some viral infections that may cause neurological signs in small animals
- Pestiviruses
- Feline infectious peritonitis (FIP)
- Canine distemper
- Borna virus
- Tick borne encephalitides
- Schmallenberg virus
What are the 3 categories of viruses that cause neurological signs
- Those causing signs in neonate following infection in utero
- Viruses causing PREDOMINANTLY neurological signs
- Viruses that MAY cause neurological signs
List the viruses that cause neurological signs in neonates
- Pestiviruses: BVD, Border disease, classical swine fever
- Parvovirus: feline panleukopaenia
- Bunyavirus: Schmallenberg virus
What is required in order for a virus to be able to cause neurological signs in the neonate following infection in utero?
- Dam must be susceptible to viral infection i.e. not vaccinated or previously exposed
- Virus must be able to cross placenta once dam is infected
Describe the neurological signs of BVD
- Minor part of BVDV and variable
- Recumbency
- Ataxia
- Blindness
- Lack of coordination
- Twtiching
- Marked intention tremor
- Signs vary depending on dose of infection and degree of response of foetus
When does infection with BVDV need to take place in order to cause neurological signs in the neonate? Explain
~d100-200 of gestation - development of cerebellum is at maximum between d130 and 160
Describe how the BVDV status of calves differs depending on when the infection occured
- After d120, foetus can mount immune response
- If before, is persistently infected and no immune response, can infect rest of herd
- Most are antibody positive and have no carrier status
What causes the neurological signs seen with in utero infection of BVDV?
Lack of cerebellum
Describe the clinical appearance of Border disease
- Early embryonic death
- Abortion
- Lambs with hairy fleece and involuntary tremor
How does in utero infection with Border disease lead to the neurological clinical signs?
Virus causes demyelination of nerve fibres in CNS, impulse coordination impaired
What is the consequence for animals infected with Border disease in utero?
Often persistently infected and need to be culled in order to prevent spread to rest of flock
Describe how an animal becomes infected with parvovirus
- Faecal oral transmission
- Persists in environment for up to a year
- Transmission by direct contact or fomites
- Infects lymph nodes of naso- and oropharynx and then spreads to other tissues
Describe the pathogenesis of parvovirus in cats
- Panleukopaenia: decreased WBC count, killing of lymphoid and myeloid stem cells, high risk of secondary infection
- Enteritis: killing of stem cells in crypts
- Cerebellar hypoplasia: infection in neonatal kittens in utero within 2 weeks of birth leads to nervous signs
Describe the presentation of kittens with in utero parvovirus infection
Control of coordination/balance lost
Outline the treatment of feline parvovirus
- Depends on severity of signs and how much owner is willing to do
- Key part is treatment of secondary infection risk
What virus is Schmallenberg and how is it transmitted?
Orthobunyavirus
- Transmitted by Culicoides mainly
Describe the clinical signs of in utero Schmallenberg virus infection
- Mainly stillbirths, abortion, congenital deformities
- Unable to suck
- Blindness
- Ataxia
Explain the pathogenesis of the neurological signs of an in utero Schmallenberg infection
- Hydrancephaly: brain replaced by sac of fluid
- Poliomyelitis: inflammation of brain and spinal cord
Give examples of viral diseases with primarily neurological signs
- Borna disease
- Tick borne encaphlitides (Louping ill, Spanish sheep encephalitis, Turkish sheep encephalitis/Greek goat encephalitis)
Which species are affected by Borna disease?
- Horses
- Cats
- Sheep
- Rabbits
- Ostrich
- Humans
Describe the pathogenesis of Borna disease
Infects neurons, cellular immune response leads to tissue destruction causing meningitis, encephalomyelitis
Describe the clinical signs of Borna disease
- Pyrexia
- Ataxia
- Pharyngeal paralysis
- Hyperaesthesia
- Fatal within several weeks
Describe the viral structure, and geographical locality of Borna disease
- Enveloped -ve sense ssRNA virus
- Endemic in upper Rhine valley area of Germany
Where do tick borne encephalitides mostly occur?
Upland, moorland areas with sparse grassland
Describe the virus that causes tick borne encephalitides
- Flaviviruses
- Enveloped +ve sense ssRNA virus
Describe the transmission of Louping ill
- Sheep-tick lifecycle
- Ticks infected when feed on viraemic animal, o tick to tick spread
- Virus replicates in gut and salivary glands of tick
- Transtadial transmission within ticks
- Bites and able to infect lots of hosts
Describe infection and clinical signs of Louping ill
- Typically lambs once MDA has waned after movement to upland pasture
- Virus infects lymph nodes then spread to other lymphoid tissue +/- CNS
- Neurological signs include tremors, exaggerated gait, death
Outline how immunosuppression affects Louping ill and give common causes
- Anaplasma phagocytophila (tick borne fever) worsens prognosis as it predisposes to secondary infections such as Staphylococcus aureus pyaemia
- Anaplasma characterised by high fever, inclusions in circulating neutrophils, reduced milk yield, abortion, reduced fertility in rams
Give examples of viruses that MAY cause neurological signs
- Canine distemper
- Feline infectious peritonitis
What is canine distemper?
Morbillivirus (Paramyxovirus)
Which dogs are most susceptible to canine distemper?
Young dogs
Describe infection with canine distemper
- transmission by direct contact
- Virus replicates in URT
- Spread to tonsils/lymph nodes
- Spills into blood stream leading to viraemia
- Viraemia and systemic spread up to epithelia of CNS
Describe the clinical signs of canine distemper
- Pyrexia, depression
- Ocular and nasal discharge
- Cough
- Vomiting and diarrhoea
- Hyperkeratosis of nose/pads (hardpad)
Outline the prognosis for canine distemper
- Solid immune response = recovery
- Poor immune response = neuro signs
- Prognosis generally guarded
Describe the treatment of canine distemper
- supportive therapy and treatment for secondary infections with antibiotics
- Fluid therapy, antibiotics
- Anticonvulsant if mild CNS signs, if severe consider euthanasia
- Interferon omega may work but not licensed, little evidence
- Rely on immune response of animal for recovery
